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Musculoskeletal simulation and dynamic modeling programs have been used to gain insight into lower-limb musculoskeletal injury mechanisms. In addition to the temporospatial, kinematic, and kinetic data obtained from motion analysis systems, musculoskeletal simulation programs also can provide information on joint contact and muscle forces, musculotendinous lengths and velocities, and muscle activation levels. Musculoskeletal simulation platforms may help in the assessment of risk factors for sports-related injuries. Using musculoskeletal simulations for injury prevention programs may help lower the incidence of sports injuries, and may allow for fast recovery from injury. In this review, injury mechanisms and risk factors of some of the most common lower-limb musculoskeletal injuries, including anterior cruciate ligament, patellofemoral, and hamstring injuries were summarized from a biomechanical perspective. Also, the efficacy of musculoskeletal modeling and dynamic simulation tools in helping our understanding of these injury mechanisms was discussed.